Enteroviruses, pancreatic beta-cells, and dendritic cells: a dangerous triangle in type 1 diabetes etiology?
Year: 2010
Type: dissertation
Abstract: Type 1 diabetes mellitus (T1D, insulin-dependent diabetes mellitus) is an endocrine autoimmune disorder in which the insulin-producing beta-cells in the pancreas are gradually destroyed. Enterovirus infections (in particular coxsackievirus and echovirus) have been implicated in the development of T1D. We set out to investigate the interplay between enteroviruses, beta-cells and dendritic cells (DCs) which are the most important antigen-presenting cells.\nWe demonstrated that human DCs can be productively infected with echoviruses (EV) but not coxsackie B viruses (CVB). Productive EV infection results in impaired DC function and causes loss of DC viability. In addition, we showed that primary CVB-infected human pancreatic islets (and also CVB-infected Min6 cells, a mouse insuloma cell line resembling pancreatic beta cells) are efficiently phagocytosed by DC. Uptake of these infected cells resulted in DC activation as indicated by the production of interferon (IFN)-alpha/beta, cytokines with strong immunomodulatory and antiviral functions, and the expression of interferon-stimulated genes. The observed innate antiviral responses depended on RNA within the phagocytosed cells, required endosomal acidification and were type I interferon (IFN)-dependent.\nWe propose a model in which enteroviruses may trigger or accelerate T1D upon infection of pancreatic beta-cells. These infected cells can be engulfed by DCs, which subsequently become activated and thereby may mediate autoimmune reactions, possibly resulting in T1D.
Author: Barbara M. Schulte
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2149642173